ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.5599C>T (p.Arg1867Trp) (rs200583769)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000256267 SCV000322843 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research 0/202 non-FH alleles
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000454967 SCV000538325 uncertain significance not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Several papers, no segs; ExAC: 0.04% (3/6614) Finnish chromosomes
Color RCV000256267 SCV000687248 uncertain significance Familial hypercholesterolemia 2017-08-06 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the beta 1 domain of the APOB protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in 2 individuals from a Spanish family diagnosed with FH (PMID 24234650) but it has also been identified in 25/121382 chromosomes by the Exome Aggregation Consortium (ExAC) general population database.
Iberoamerican FH Network RCV000256267 SCV000748124 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Color RCV000775211 SCV000909454 uncertain significance Familial hypercholesterolemias 2018-05-15 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant (also known as p.Arg1840Trp in the mature protein) is located in the beta 1 domain of the APOB protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in two individuals from a Spanish family diagnosed with familial hypercholesterolemia (PMID: 24234650) but it has also been identified in 51/276966 chromosomes (40/126508 non-Finnish European chromosomes) by Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000793138 SCV000932478 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Hypobetalipoproteinemia, familial, 1 2018-10-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1867 of the APOB protein (p.Arg1867Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs200583769, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual affected with familial hypercholesterolemia (PMID: 24234650). ClinVar contains an entry for this variant (Variation ID: 265887). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.